Facilitated antigen presentation and its inhibition by blocking IgG antibodies depends on IgE repertoire complexity

Abstract

The antibody repertoires of allergic subjects are characterized by the presence of allergen-specific IgE antibodies. We have previously shown that the composition of the IgE repertoire is critical for allergen-mediated activation of human effector cells. Activation of CD4(+) T cells in allergic subjects is highly potentiated by the process of facilitated antigen presentation (FAP), in which allergen in complex with IgE is taken up by B cells through the low-affinity IgE receptor CD23 and presented to T cells. We sought to investigate the influence of IgE repertoire complexity on the formation of IgE/allergen/CD23 complexes on B cells and subsequent T-cell activation. Using defined allergen-specific recombinant IgE and IgG antibodies, we investigated the influence of individual IgE affinity, IgE clonality, specific IgE concentration, and the ratio between IgE specificities on IgE/allergen/CD23 complex formation in vitro. Although IgE affinity is an important factor, IgE clonality seems to be governing complex formation, especially with medium- and low-affinity IgE antibodies. We demonstrate that differences in allergen-specific IgE affinity correlate with the efficiency of subsequent T-cell activation. In addition, we show that the complexity of an IgE repertoire also affects the ability of allergen-specific IgG antibodies to block FAP. The composition of allergen-specific IgE repertoires in individual patients, especially with respect to IgE clonality, might play an important role in the manifestation of allergic disease not only for the immediate allergic reaction through activation of basophils and mast cells but also for the exacerbation of allergic inflammation through recurring activation of allergen-specific T cells by FAP.